BACKGROUND:Many epidemiological studies have investigated the prevalence of type 2 diabetes in individuals with a psychiatric disorder. In an umbrella review, we aim to systematically summarize existing systematic reviews examining the prevalence of type 2 diabetes in people with a psychiatric disorder. When information is available in the identified systematic reviews, comparisons with control groups without a psychiatric disorder will be made. Furthermore, we aim to assess the quality of the included systematic reviews.METHODS:The umbrella review will be based on a comprehensive systematic search of systematic reviews of observational (cross-sectional or longitudinal) studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. Four electronic databases (Embase, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews) will be searched. Retrieved papers will be screened for eligibility by two independent reviewers. Furthermore, the reference lists of all included publications will be screened. Data will be extracted by using an a priori developed data extraction form and two independent reviewers will assess the risk of bias in the included systematic reviews using with the Risk of Bias in Systematic Reviews (ROBIS) tool. A narrative data-synthesis and a subsequent meta-analysis based on the primary studies will be made.DISCUSSION:For each psychiatric disorder, the data regarding the prevalence of type 2 diabetes will be summarized and discussed. When possible, comparisons with control groups will be reported and discussed. Finally, future implications and recommendations for clinical care will be presented.SYSTEMATIC REVIEW REGISTRATION:This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on December 9, 2019 (registration number: pending).

Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and “at risk” individuals, was undertaken to determine GE's contribution to glucose homeostasis. GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic “at risk” relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in “at risk” individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in “at risk” individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. In “at risk” individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state.

Physiology EducationUndergraduate Physiology Degree Programs in the United States: from Famine to FeastErik J. HenriksenErik J. HenriksenUniversity of Arizona College of Medicine, Tucson, ArizonaPublished Online:01 Jul 2015https://doi.org/10.1152/physiol.00015.2015MoreSectionsPDF (44 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat The formal teaching of physiology and physiology-related subjects at the undergraduate level in colleges and university in the U.S. is critical for the long-term success of this important area of science. This educational endeavor is a fundamental requirement for the continued movement of students through the “physiology pipeline,” ultimately producing the next generation of physiologists prepared to perform research, teaching, and service in this field (1). Moreover, the teaching of physiology at the undergraduate level makes important contributions to the preparation of students for post-baccalaureate training in a variety of health professions. The overarching goals of this editorial are to provide a perspective of the history and status of undergraduate programs in the U.S. that award a bachelors of science (BS) degree in physiology, to briefly touch on the aspirations of students who choose to pursue a degree in physiology, and to outline the challenges that face existing and future undergraduate physiology degree programs in this country.The Evolution of Undergraduate Physiology ProgramsAt the beginning of the 21st century, only a handful of established undergraduate degree programs awarding BS degrees in physiology (or physiological sciences) existed at universities in the U.S. These included well known, sizable programs at UCLA, Michigan State University, and the University of Arizona. Since that time, impressive growth in the number of programs awarding BS degrees in physiology has taken place. By 2006, when the American Physiological Society organized a summit to discuss strategies to promote the teaching of physiology at colleges and universities (2), 10 programs awarding a BS or a bachelor of arts (BA) in physiology had been identified. In 2014, Wehrwein and colleagues (4) described 15 undergraduate programs offering BS degrees in physiology, integrative physiology, or human physiology. Many, if not most, of these physiology programs evolved from what had previously been kinesiology/exercise science programs. In addition, they identified 23 undergraduate degree programs in biology with an emphasis, concentration, or specialization in physiology, and 3 programs offering a bachelors degree in neuroscience/neurobiology combined with physiology (4). It is clear that the number of undergraduate programs offering degrees in physiology or an emphasis/concentration/specialization in physiology has increased tremendously over the last 15 years.In addition to the increased number of domestic undergraduate programs offering BS degrees in physiology since 2000, enrollments in these physiology majors have also exploded during this time period. The physiology major at the University of Arizona College of Medicine is a prime example of this development (3). In 2000, there were 467 undergraduates enrolled in this program. This number increased to 1,260 by 2007, and by 2014 the number of physiology majors at the University of Arizona had reached 2,064, more than a fourfold increase since 2000. Impressive increases in enrollments in physiology programs have been experienced in other programs, such as the Integrative Physiology Program at the University of Colorado-Boulder (from 675 majors in 2003 to 1,916 in 2014) (Enoka R, personal communication), the BS in Human Physiology Program at the University of Iowa (from 175 in 2010 to 930 in 2014) (Kregel K, personal communication), the Human Physiology Program at the University of Oregon (from 254 in 2003 to 1,142 in 2014) (Halliwill J, personal communication), the Physiology and Human Biology Program at Michigan State University (from ∼700 in 2000 to over 1,600 in 2014) (Wehrwein E, personal communication), and the Human Physiology Program at Gonzaga University, a small, private institution (from 116 in 2009 to 162 in 2014) (McCann D, personal communication). In general, the growth of these physiology programs has far exceeded the increases observed in overall undergraduate enrollments at these institutions.The Physiology Undergraduate Degree CurriculumWhile there is no standardization of the curriculum in undergraduate physiology degree programs in the U.S., and there is no accrediting body for these programs, in general there are several common features in the course requirements of most domestic physiology undergraduate degree programs. These curricular requirements have been meticulously assessed by Erica Wehrwein and James Poteracki at Michigan State University (Ref. 4; and personal communications). A comprehensive discussion of the various curricular requirements of domestic undergraduate physiology degree programs is beyond the scope of this editorial. In brief, however, most physiology programs awarding the BS degree require up to two semesters of basic human anatomy and physiology lecture courses and laboratories, and several programs require upper division courses in cellular physiology, biochemistry, or genetics. Moreover, most of these programs have basic requirements in mathematics (up to calculus II or statistics), introductory biology, general and organic chemistry, and physics. All programs require successful completion of several upper division elective courses covering a wide variety of physiology specialty topics.Aspirations of Physiology Undergraduate MajorsThe vast majority of undergraduates enrolled in physiology degree programs have a long-term interest in a health profession, which requires substantial additional post-baccalaureate professional training. In 2013, we surveyed students at the University of Arizona graduating with a BS degree in physiology regarding their professional aspirations (Stanescu C, personal communication). Almost half indicated a desire to become a medical doctor (46%, with no differentiation between allopathic and osteopathic medicine). Other professional aspirations included physician assistant (15%), attaining a doctorate or Masters degree in a biological science (12%), physical therapy (10%), dentistry (4%), doctor of pharmacy (3%), optometry (2%), or various other professions (8%). These results generally confirmed those from a previous survey we conducted in 2010 (3). Informal conversations with faculty associated with other large domestic undergraduate physiology degree programs (e.g. Michigan State University, University of Colorado, University of Iowa, University of Oregon) have revealed that their students share these same general professional aspirations.Future Challenges for Undergraduate Physiology ProgramsOver the past 15 years, key academic departments at American universities have met the challenge of increasing the availability and capacity of programs designed to meet the needs of undergraduates seeking a BS degree in physiology. A key question that must be addressed at present and in the coming years is: Can the development of new physiology degree programs and the expansion of established undergraduate physiology programs continue to accommodate this ever expanding demand? There are numerous factors at work that will make this a challenging task. First, these departments will need to hire additional faculty, both in the tenure track and in the lecturer track, to be able to provide instructors for the coursework that these programs demand. In light of retirements in an aging faculty population in many of these programs, this will be an especially demanding task. Second, with increasing enrollments in these programs, increased class sizes and additional sections of courses will be necessary, and the issue of classroom availability to meet these expanding needs will be challenging for many institutions. The prospect of online courses to meet this demand certainly merits discussion. Third, many institutions may have issues finding appropriate laboratory space for additional sections of large core courses, such as human anatomy and physiology. Finding well trained ancillary personnel to run these laboratory sections, such as graduate teaching assistants and adjunct faculty, may be problematic. Fourth, there must be financial resources to pay for all of this, and an overriding issue at hand is the trend in many states for continued substantial reductions in financial support for their public university systems.A final challenge relates to the question of whether these students actually achieve their professional goals following graduation with a BS degree in physiology. The general consensus among faculty associated with large undergraduate physiology programs is that an accurate determination of the professional outcomes of their graduates is an extremely difficult task. Anecdotal evidence indicates that many students ultimately do attain their post-graduation goals using their excellent physiology backgrounds. However, a critical challenge for undergraduate physiology programs will be the implementation of evidence-based strategies for determining the actual professional outcomes of these numerous physiology graduates.In closing, it is clear that the demand for these undergraduate physiology degree programs in the U.S. remains very high, and institutions of higher education will continue to make every effort to create and expand programs to meet this demand for broad-based physiology education.FOOTNOTESThe author thanks Dr. Nicholas Delamere for a critical review of this editorial.No conflicts of interest, financial or otherwise, are declared by the author(s).References1. American Physiological Society. Toward a strategic plan: summary of APS Strategic Planning Meeting. The Physiologist 54: 113–120, 2011.Google Scholar2. Carroll R, Matyas M, Atwater AE, Doze V, Faircloth R, Finkenstadt P, Goodman B, Henriksen EJ, Horwitz B, Looft-Wilson R, Madsen B, Mody J, Pelaez N, Pressley T. APS undergraduate brainstorming summit report. Adv Physiol Educ 31: 380–386, 2007.Link | Google Scholar3. Henriksen EJ, Atwater AE, Delamere NA, Dantzler WH. The physiology undergraduate major in the University of Arizona College of Medicine: past, present, and future. Adv Physiol Educ 35: 103–109, 2011.Link | ISI | Google Scholar4. Wehrwein EA, Poteracki JM, McCann DJ, Henriksen EJ, Matyas ML, Halliwill JR. A nationwide assessment and comparison of curriculum requirements in undergraduate physiology programs. The Physiologist 57: 353, 2014.Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByThe case for coordinating efforts to establish program guidelines and strengthen physiology undergraduate degree programsErica A. Wehrwein, Lisa C. Anderson, Anne R. Crecelius, Claudia I. Stanescu, James M. Poteracki, John R. Halliwill, Nancy Aguilar-Roca, and Jennifer Rogers29 September 2020 | Advances in Physiology Education, Vol. 44, No. 4A brief history of the Physiology Majors Interest Group (P-MIG)Erica A. Wehrwein, James M. Poteracki, and John R. Halliwill29 September 2020 | Advances in Physiology Education, Vol. 44, No. 4Professional skills for physiology majors: defining and refiningMichelle B. French, Julia K. Choate, John Zubek, Randy W. Bryner, Kathryn M. S. Johnson, and Meredith J. Luttrell29 September 2020 | Advances in Physiology Education, Vol. 44, No. 4 More from this issue > Volume 30Issue 4July 2015Pages 254-255 Copyright & Permissions©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.https://doi.org/10.1152/physiol.00015.2015PubMed26136537History Published online 1 July 2015 Published in print 1 July 2015 Metrics

Program assessment is a challenging task, especially in the Physiology Undergraduate major at the University of Arizona, which must accommodate over 2000 students in large classrooms. We describe an assessment plan that includes six student learning outcomes (SLOs). Students are expected to demonstrate knowledge of cellular (SLO 1) and organ systems function (SLO 2); show the ability to integrate knowledge from the cellular and molecular to the organ system level of organization (SLO 3); effectively read, evaluate and communicate scientific information (SLO 4); conduct and/or evaluate physiology laboratory experiments (SLO 5); and demonstrate knowledge of current physiology topics (SLO 6). Faculty have developed a sustainable assessment program that includes direct and indirect measures of assessment and is being implemented over a four‐year period. The first year included assessment of SLOs 1, 2, and 3 that will be measured annually. SLOs 4, 5, and 6 will be evaluated in subsequent years on a rotating basis. Assessment activities include: 1) pre‐post clicker questions in large core courses that determine cellular and organ systems knowledge (SLOs 1, 2); 2) use of a grading rubric to assess the ability to integrate physiology in a subsample of graduating seniors participating in a focus group (SLO 3); 3) use of a grading rubric on a subsample of students in a large advanced elective course to evaluate the ability to effectively communicate scientific information (SLO 4); and 4) graduating senior surveys to obtain student ratings for program SLOs, major courses, advising and overall satisfaction with the Physiology major. The overall goal is to collect and analyze data, discuss findings with the faculty, refine the curriculum as needed, and regularly improve the assessment plan.

BACKGROUND AND PURPOSE: In patients with hypertension, medication adherence is often suboptimal, thereby increasing the risk of ischemic heart disease and stroke. In a randomized trial, we investigated the effectiveness of a multifaceted pharmacist intervention in a hospital setting to improve medication adherence in hypertensive patients. Motivational interviewing was a key element of the intervention.METHODS: Patients (n = 532) were recruited from 3 hospital outpatient clinics and randomized to usual care or a 6-month pharmacist intervention comprising collaborative care, medication review, and tailored adherence counseling including motivational interviewing and telephone follow-ups. The primary outcome was composite medication possession ratio (MPR) to antihypertensive and lipid-lowering agents, at 1-year follow-up, assessed by analyzing pharmacy records. Secondary outcomes at 12 months included persistence to medications, blood pressure, hospital admission, and a combined clinical endpoint of cardiovascular death, stroke, or acute myocardial infarction.RESULTS: At 12 months, 20.3% of the patients in the intervention group (n = 231) were nonadherent (MPR <0.80), compared with 30.2% in the control group (n = 285) (risk difference -9.8; 95% confidence interval [CI], -17.3, -2.4) and median MPR (interquartile range) was 0.93 (0.82-0.99) and 0.91 (0.76-0.98), respectively, P = .02. The combined clinical endpoint was reached by 1.3% in the intervention group and 3.1% in the control group (relative risk 0.41; 95% CI, 0.11-1.50). No significant differences were found for persistence, blood pressure, or hospital admission.CONCLUSIONS: A multifaceted pharmacist intervention in a hospital setting led to a sustained improvement in medication adherence for patients with hypertension. The intervention had no significant impact on blood pressure and secondary clinical outcomes. (C) 2015 Elsevier Inc. All rights reserved.

The risk of cardiovascular disease is markedly elevated in individuals with diabetes, representing the primary cause of morbidity and mortality in these diabetic patients (1). More specifically, individuals with diabetes display dysfunctions in the regulation of blood flow in coronary arterioles (2,3). Importantly, impairments in the appropriate vasodilatory response of myocardial arterioles to various pharmaceutical and physical stimuli can be present even if there is no discernible atherosclerotic blockage in these blood vessels (4,5). Moreover, increased flow-mediated dilation (FMD) in coronary arterioles is an important regulatory mechanism for controlling arteriolar diameter and blood flow in response to changes in wall shear stress, and this mechanism is also impaired in conditions of glucose dysregulation (6,7). While the underlying etiology for the dysfunctions in the coronary microcirculation in diabetes is certainly multifactorial, the contribution of impairments in the endothelial nitric oxide (NO)–generating system and their association with the excess generation of reactive oxygen species (ROS) appears to be crucial in the development of these vascular abnormalities. For example, the impairment of the induction of vasodilation in coronary arterioles in the db/db mouse, a model of obesity-associated insulin resistance and type 2 diabetes, is related to limitations in NO availability (8,9). It is of great interest that NO availability can be compromised by interactions with superoxide anion, with a …

AIMS:Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness in the development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release.METHODS:At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined.RESULTS:At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs developed raised fasting and 2-hour OGTT glucose. FG10y correlated significantly with FG0y and body mass index0y and negatively with √GE and 2-hour OGTT glucose10y with FG0y and negatively with AIRIVGTT0y and AIROGTT0y. Log AIROGTT10y correlated with √GE, log AIRIVGTT0y and log AIROGTT0y. Multiple regression analyses demonstrated the following: REL FG10y was predicted by combined FG0y, √GE and body mass index0y (radj(2) = 56%; P ≤ .001) and 2-hour OGTT glucose10y weakly related by FG0y,and √GE (r(adj)(2) = 25%; P = .06). Log AIROGTT10y was predicted by AIRIVGTT0y and √GE (r(adj)(2) = 46%; P ≤ .004).CONCLUSION:In normoglycemic RELs, a relative reduction of glucose effectiveness is an important contributor over 10 years to the development of isolated impaired fasting glucose and reduced acute insulin secretion.

Issue In Denmark, patients who do not speak Danish are entitled to assistance of an interpreter when having a consultation in the public health care system. With the aim of reducing costs and increasing the quality of the interpretation, a nation-wide project has introduced video interpretation in Danish hospitals.Description of the study An American study shows that the amount of time health professionals spend in consultations involving an interpreter decreases significantly when face-to-face …

Hydrogen peroxide (H2O2) is an important regulator of cellular events leading to glucose transport activation in mammalian skeletal muscle. In the absence of insulin, H2O2 in the low micromolar range engages the canonical IRS-1/PI3K/Akt-dependent insulin signaling pathway, as well as other signaling elements (AMPK and p38 MAPK), to increase basal glucose transport activity. In contrast, in the presence of insulin, H2O2 antagonizes insulin signaling by recruitment of various deleterious serine/threonine kinases, producing a state of insulin resistance. Here, we describe the H2O2 enzymatic-generating system, utilizing glucose oxidase, that has been used to investigate the impact of H2O2 on cellular signaling mechanisms related to glucose transport activity in isolated rat skeletal muscle preparations, such as the soleus. By varying the glucose oxidase concentration in the medium, target ranges of steady-state H2O2 concentrations (30-90 μM) can be attained for up to 6h, with subsequent assessment of cellular signaling and glucose transport activity.

Angiotensin receptor (type 1) blockers (ARBs) can reduce both hypertension and insulin resistance induced by local and systemic activation of the renin-angiotensin-aldosterone system. The effectiveness of azilsartan medoxomil (AZIL-M), a novel imidazole-based ARB, to facilitate metabolic improvements in conditions of angiotensin II (Ang II)-associated insulin resistance is currently unknown. The aim of this study was to determine the impact of chronic AZIL-M treatment on glucose transport activity and key insulin signaling elements in red skeletal muscle of Ang II-treated rats. Male Sprague-Dawley rats were treated for 8 weeks with or without Ang II (200 ng/kg/min) combined with either vehicle or AZIL-M (1 mg/kg/day). Ang II induced significant (p < 0.05) increases in blood pressure, which were completely prevented by AZIL-M. Furthermore, Ang II reduced insulin-mediated glucose transport activity in incubated soleus muscle, and AZIL-M co-treatment increased this parameter. Moreover, AZIL-M treatment of Ang II-infused animals increased the absolute phosphorylation of insulin signaling molecules, including Akt [both Ser473 (81%) and Thr308 (23%)] and AS160 Thr642 (42%), in red gastrocnemius muscle frozen in situ. Absolute AMPKα (Thr172) phosphorylation increased (98%) by AZIL-M treatment, and relative Thr389 phosphorylation of p70 S6K1, a negative regulator of insulin signaling, decreased (51%) with AZIL-M treatment. These results indicate that ARB AZIL-M improves the in vitro insulin action on glucose transport in red soleus muscle and the functionality of the Akt/AS160 axis in red gastrocnemius muscle in situ in Ang II-induced insulin-resistant rats, with the latter modification possibly associated with enhanced AMPKα and suppressed p70 S6K1 activation.

The condition of oxidative stress arises when oxidant production exceeds antioxidant activity in cells and plasma. The overabundance of oxidants is mechanistically connected to the multifactorial etiology of insulin resistance, primarily in skeletal muscle tissue, and the subsequent development of type 2 diabetes. Two important mechanisms for this oxidant excess are (1) the mitochondrial overproduction of hydrogen peroxide and superoxide ion under conditions of energy surplus and (2) the enhanced activation of cellular NADPH oxidase via angiotensin II receptors. Several recent studies are reviewed that support the concept that direct exposure of mammalian skeletal muscle to an oxidant stress (including hydrogen peroxide) results in stimulation of the serine kinase p38 mitogen-activated protein kinase (p38 MAPK), and that the engagement of this stress-activated p38 MAPK signaling is mechanistically associated with diminished insulin-dependent stimulation of insulin signaling elements and glucose transport activity. The beneficial interactions between the antioxidant α-lipoic acid and the advanced glycation end-product inhibitor pyridoxamine that ameliorate oxidant stress-associated defects in whole-body and skeletal-muscle insulin action in the obese Zucker rat, a model of prediabetes, are also addressed. Overall, this review highlights the importance of oxidative stress in the development of insulin resistance in mammalian skeletal muscle tissue, at least in part via a p38-MAPK-dependent mechanism, and indicates that interventions that reduce this oxidative stress and oxidative damage can improve insulin action in insulin-resistant animal models. Strategies to prevent and ameliorate oxidative stress remain important in the overall treatment of insulin resistance and type 2 diabetes.

The impact of the lipid peroxidation end‐product, reactive aldehyde, and oxidant 4‐hydroxynonenal (4‐HNE) on the glucose transport system in rat slow‐twitch skeletal muscle is currently unknown. Therefore, we assessed the effect of 4‐HNE on insulin signaling (IRS proteins and phosphorylation of Akt Ser473 (pAkt) and AS160 Thr642 (pAS160)) and glucose transport in slow‐twitch muscle. Soleus strips from lean Zucker rats were incubated with 4‐ HNE (50 μM) for up to 6 hr. Insulin‐stimulated (5 mU/ml) glucose transport was decreased by 4‐HNE at 2 hr (30%), 4 hr (26%), and 6 hr (39%) (p<0.05). At 2 hr of 4‐HNE treatment with insulin, pAS160 was decreased by 28%, whereas pAkt was only reduced by 11% and IRS‐1 protein was not changed. At 4 hr, pAS160 and pAkt were decreased by 22% and IRS‐1 was 39% lower. At 6 hr, pAS160 was 47% lower, pAkt was decreased by 26%, and IRS‐1 protein was reduced by 51%. Interestingly, IRS‐2 was slightly decreased (17%) only at 6 hr. These data indicate that the lipid peroxidation end‐product and oxidant 4‐HNE induces insulin resistance of glucose transport activity in rat slow‐twitch skeletal muscle, associated initially with impaired AS160 phosphorylation and subsequently with impaired Akt phosphorylation and selective loss of IRS‐1 protein. These results provide further support for an important role of lipid‐derived oxidative stress in the etiology of skeletal muscle insulin resistance.

) A)primary)defect)leading)to)the)development)of)type)2)diabetes)is)insulin)resistance)of)the) glucose)transport)system)in)skeletal)muscle.))One)factor)known)to)induce)insulin)resistance)is) oxidative)stress.))A)by>product)of)lipid)peroxidation)is)the)reactive)aldehyde)4>hydroxynonenal)(4> HNE),)an)oxidant)that)induces)a)number)of)deleterious)consequences)on)cell)function.))However,)the) impact)of)4>HNE)on)the)glucose)transport)system)in)rat)slow>twitch)skeletal)muscle)is)currently)not) known.))Therefore,)we)assessed)the)impact)of)4>HNE)on)insulin)signaling)factors)(IRS>1)protein) expression)and)phosphorylation)of)Akt)Ser473)(pAkt))and)AS160)Thr642)(pAS160)))and)on)glucose) transport)activity)in)mammalian)slow>twitch)muscle.))Strips)of)soleus)muscle)from)lean)Zucker)rats) were)incubated)with)4>HNE)(50)μM))in)the)absence)or)presence)of)insulin)(5)mU/ml))for)up)to)6)hr.)) Insulin>stimulated)glucose)transport)activity)(determined)using)2>deoxyglucose)uptake))was) decreased)by)4>HNE)at)2)hr)(30%),)4)hr)(26%),)and)6)hr)(39%))(all)p HNE) treatment)in)the)presence)of)insulin,)pAS160)was)decreased)by)28%,)whereas)pAkt)was)only)reduced) 11%)and)IRS>1)protein)levels)were)not)changed.))At)4)hr,)pAS160)was)decreased)by)22%,)as)was) pAkt,)and)IRS>1)levels)were)39%)lower)than)in)the)control)muscles.))At)6)hr,)pAS160)was)47%)lower,) pAkt)was)decreased)by)26%,)and)IRS>1)protein)levels)were)reduced)by)51%.))Interestingly,)IRS>2) protein)levels)were)decreased)by)17%)only)at)the)6)hr)time)point.))In)summary,)these)data)indicate) that)the)lipid)peroxidation)end>product)and)oxidant)4>HNE)induces)insulin)resistance)of)glucose) transport)activity)in)rat)slow>twitch)skeletal)muscle,)initially)associated)with)impaired) phosphorylation)(and)therefore)reduced)activation))of)AS160.))Longer)durations)of)4>HNE)exposure) led)to)a)greater)impairment)of)Akt)phosphorylation)and)to)a)selective)loss)of)IRS>1)protein.))These) results)provide)further)support)for)an)important)role)of)oxidative)stress)in)the)etiology)of)skeletal) muscle)insulin)resistance.)